Acetogenins, an important class of compounds containing tetrahydrofuran ring systems, were isolated from Annonaceae plants. They are known to exhibit a wide range of biological activities such as antifeedant, antitumor, immunosuppressive and most significantly pesticidal and pheromonal activities. This interesting biological profile along with varied structural features of the acetogenin family has aroused a lot of research interest in the synthesis of this class of compounds among organic chemists worldwide.
Petromyroxol is a tetrahydrofuran diol from the acetogenin family and one of the vast array of natural compounds that contain a tetrahydrofuran. Petromyroxol was known to have a possible biochemical role in the study of communication among sea lamprey, which are parasitic fish that have been known to cause damage to the fish population especially in the Great lakes area of North America.
The Li and co-workers reported the isolation of a pair of enantiomers from water conditioned with larval Sea Lamprey (Petromyzonmarinus) (Org. Lett. 2015, 17, 286-289). One of the enantiomers named (+)-petromyroxol (1) showed promising olfactory response in the concentration range of 0.01 to 1 uM. Sea Lamprey is an aggressive predator of trout populations. It is found mainly in the northern Atlantic Ocean and in the western Mediterranean Sea and the main concern is that Sea Lamprey is an invader of the Laurentian Great Lakes which hold nearly 20% of the world's supply of freshwater. Thus there has been a massive research effort on how to control this pest.
Article titled “Enantioselective Synthesis of (+)-Petromyroxol, Enabled by Rhodium-Catalyzed Denitrogenation and Rearrangement of a 1-Sulfonyl-1,2,3-Triazole” by A Boyer published in J. Org. Chem., 2015, 80 (9), pp 4771-4775 reports enantioselective synthesis of (+)-Petromyroxol using by Rhodium-Catalyzed Denitrogenation and Rearrangement of a 1-Sulfonyl-1,2,3-Triazole in 9 steps and 20% overall yield.
Article titled “Total Synthesis of (+)-Petromyroxol, a Marine Natural Product” by S Gahalawat et al. published in Asian Journal of Organic Chemistry, 2015, 4 (10), pp 1025-1029 reports an efficient total synthesis of (+)-petromyroxol, by using Sharpless asymmetric dihydroxylation (AD), intramolecular SN2 cyclization and stereoselective Grignard reaction as key steps.
Article titled “Total synthesis of (+)-petromyroxol via tandem α-aminoxylation-allylation and asymmetric dihydroxylation-SN2 cyclization approach” by U Nookaraju et al. published in RSC Adv., 2015,5, pp 63311-63317 reports the total synthesis of (+)-petromyroxol, a tetrahydrofuran (THF)-diol fatty acid, by using a tandem α-aminoxylationallylation, cross metathesis and tandem asymmetric dihydroxylation-SN2 cyclization as key steps.
The construction of stereochemically defined THF ring has always been a major challenge which is evident from various literature reports. The attractive structural features of petromyroxol along with biological importance and its low abundance drew researcher's attention towards its synthesis. Accordingly, the present invention directed towards an enantioselective process for synthesis of (+)-petromyroxol and its three distereomers by varying the stereochemistry mainly at C5 and/or C6.